Recent advances in basic research techniques have led to an explosion of information and interest in the role of gastrointestinal peptides in health and disease. The function of these peptides has been shown to extend beyond their classical role as hormones to include actions as paracrine effectors, neurotransmitters, growth factors and cytokines. Peptides are well known to have a myriad of actions in the gastrointestinal tract, but also to have profound influences on the function of most of the body's organ systems. The ubiquitous distribution and myriad actions of gut peptides served as the catalyst that culminated in the formation of the University of Michigan Gastrointestinal Peptide Research Center;a successful multidisciplinary group of investigators that crosses traditional clinical disciplines and scientific boundaries. Advances in cell biology, biochemistry, and molecular biology have provided tools with which the genetic or molecular links between peptides and clinically relevant disorders of digestive function may be identified. The Center, through its Core laboratories and support of innovative Pilot/Feasibility projects, has provided expertise, technical and financial support that enables investigators to broaden the scope of their research. The 3 major thematic areas that reflect the common research Interests of numerous investigators affiliated with the Center remain unchanged. These include 1) Neurobiology in Appetite Control and Visceral Pain, 2) Molecular and Cellular Mechanisms of Inflammation, and 3) Cell Growth Differentiation and Program Cell Death. We have expanded our research in neurobiology in appetite control to include a new but related area which addresses peptide regulation of energy balance and metabolism. For research in inflammation, we plan to add a new Microbiome Core which is important to study host immunity and mucosal inflammation. The addition of Tom Wang and his program project on the use of confocal microendoscopy for early detection of Gl malignancy will enhance translational research in neoplastic cell growth. In response to advances in new technologies we have streamlined our core laboratories into 1.) molecular biology;2.) protein identification and localization core;3.) microbiome and inflammation and 4.) In vivo studies. Because most of the research involving cell imaging is to localize and characterize intracellular proteins, the Cell Biology Core is now combined with the Peptide and Proteomics Core. Proteins will be identified by mass spectrometry and their intracellular locations determined by immunohistochemistry and confocal fluorescence microscopy. The purpose of the new Microbiome Core is to provide Center investigators access to state of the art techniques for analysis of host/miorobiome interactions. The Peptide Center has galvanized the activities of a large number of researchers who investigate the actions of gut peptides at the University of Michigan, as well as attract new investigators to this field of research. Through the current application, we are seeking to continue and expand the Center with the hope that together the group will approach questions of fundamental importance in the pathophysiology, diagnosis, and treatment of Gl disorders in man.